Human Heart Can Make New Cells

THURSDAY April 2, 2009 -- Solving a longstanding mystery, scientists have found that the human heart continues to generate new cardiac cells throughout the life span, although the rate of new cell production slows with age.

The finding, published in the April 3 issue of Science, could open a new path for the treatment of heart diseases such as heart failure and heart attack, experts say.

"We find that the beating cells in the heart, cardiomyocytes, are renewed," said lead researcher Dr. Jonas Frisen, a professor of stem cell research at the Karolinska Institute in Stockholm, Sweden. "It has previously not been known whether we were limited to the cardiomyocytes we are born with or if they could be renewed," he said.

The process of renewing these cells changes over time, Frisen added. In a 20-year-old, about 1 percent of cardiomyocytes are exchanged each year, but the turnover rate decreases with age to only 0.45 percent by age 75.

"If we can understand how the generation of new cardiomyocytes is regulated, it may be potentially be possible to develop pharmaceuticals that promote this process to stimulate regeneration after, for example, a heart attack," Frisen said.

With this finding, scientists are "opening the door to potential therapies to having ourselves heal ourselves," Bhardwaj said. "Maybe one could devise a pharmaceutical agent that would make heart cells make new and more cells to overcome the problem they are facing."

But roadblocks remain. According to Bhardwaj, scientists do not yet know how to increase heart cell production to a rate that would replace cells faster than they are dying off, especially in older patients with heart failure. In addition, the number of new cells the heart produces was estimated using healthy hearts -- whether the rate of cell turnover in diseased hearts is the same remains unknown.

To find out the rate at which new heart cells are generated, the researchers used carbon-14 dating to estimate exactly when in the life span the cells were created. They found that less than 50 percent of cardiomyocytes are exchanged during a normal human life span.

Levels of carbon-14 can be used to date the cells, because levels of this isotope rose during the era of above-ground nuclear bomb tests, back in the 1950s. This also increased the levels of carbon-14 in the cells of all people and animals on Earth at the time. However, the levels of carbon-14 in our DNA has been dropping since above-ground testing was banned. So, pinpointing the levels of carbon-14 at various times in particular cells let the researchers date when each cell was born.

Dr. Gregg C. Fonarow, a professor of cardiology at the University of California, Los Angeles, said that for any cell-replacement therapy to be clinically useful, the rate of cell regeneration would have to dramatically increase.

"It was previously believed that the cardiomyocytes are terminally differentiated and cannot regenerate when the heart is damaged," Fonarow said. "Recent studies have suggested that cardiomyocytes can regenerate, but there has been substantial controversy as to the rate of cellular turnover," he said.

This new study, using carbon dating, suggests that cardiomyocyte regeneration can occur, but to a very limited degree, Fonarow said.

"Whether there will be medical or gene therapies that can safely and effectively allow for higher rates of myocardial regeneration will require further study," he said.

In a related development, scientists reporting in the April 3 issue of Cell Stem Cell found that they could use stem cells to promote the creation of new blood vessels in mouse hearts.

The team from Ludwig-Maximilians University, Munich, used a dual therapy. On one side, they slowed the degradation of SDF-1, the main chemical that guides stem cells to damaged heart tissue. They also treated the mouse hearts with granulocyte colony stimulating factor, a drug that mobilizes stem cells from various places such as the bone marrow and blood. This two-pronged approach led to the generation of new blood vessels and improved cardiac function following a heart attack, the team said.

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